Despite 25 years of prevention efforts, the HIV epidemic continues among men who have sex with men (MSM), highlighting the urgent public health need for testing new approaches to prevent HIV. Multiple studies have shown that methamphetamine (meth) use is a driving force in the MSM HIV epidemic. We believe the time has come to test the acceptability and feasibility of pharmacologic interventions to reduce meth use among sexually active, meth-dependent MSM, whose meth-associated sexual behavior places them at extraordinarily high risk for transmitting or acquiring HIV. In this pilot study, we will provide meth- dependent MSM with placebo or daily bupropion XL (extended-release), a well-tolerated dopamine agonist that has potential to reduce meth use. The specific aims of this study are: 1) To assess the feasibility of enrolling and retaining meth-dependent MSM into a randomized, double-blind study of bupropion versus placebo with biologic (urine meth testing) and behavioral (sexual risk) measures. 2) To explore the tolerability of bupropion and placebo among meth-dependent MSM, as determined by the number of adverse clinical events in the bupropion and placebo arms. 3) To describe the acceptability of bupropion and placebo among meth-dependent MSM by measuring (via electronic pill caps) medication adherence to bupropion and placebo. 4) To explore the potential for bupropion to reduce meth use significantly more than placebo, as determined by the proportion of meth-negative urines in the bupropion versus placebo arms. We will enroll 30 meth-dependent, sexually active MSM who will be randomized to receive bupropion or placebo for 90 days. Study results will be used to design phase III clinical trials to determine the efficacy of pharmacologic agents in reducing meth use and corresponding meth-associated sexual risk. This pilot study is therefore designed to reflect the structure of an efficacy trial and will provide data to estimate the required sample size of future efficacy studies. We include medical safety parameters as required by the Food and Drug Administration when testing a medication for a new indication in a new population. We include both urine testing and behavioral risk assessments because we anticipate that future efficacy trials will include an HIV prevention focus, analyzing not only substance use but also sexual risk behavior outcomes. [unreadable] [unreadable]